Corn residues are an abundant and low-cost lignocellulosic feedstock that provides a renewable carbon platform for the production of biofuels, bioplastics, and high-value aromatic volatile compounds (AVCs). Isoamyl alcohol, an important AVC, has applications in the food, cosmetics, and biofuel industries. This study evaluated the bioconversion of corn cob acid hydrolysates by Meyerozyma guilliermondii into isoamyl alcohol and ethanol. Corn cob was selected as feedstock due to its high hemicellulose content. A Box–Behnken (BBD) design was used to optimize phosphoric acid hydrolysis. The optimal treatment (2.49% v/v H₃PO₄, 130 °C, 120 min, 1 mm particle size) generated 19.79 g L⁻¹ xylose with 2.74 g L⁻¹ acetic acid. Then, agitation speed and nitrogen concentration were optimized via a central composite design (CCD) in synthetic and hydrolysate-based media fermentations. Isoamyl alcohol specific yield after 48 h of fermentation was higher in hydrolysate medium (12.08 ± 0.67 mg·g⁻¹) than in synthetic medium (8.274 ± 0.83 mg·g⁻¹). Free amino nitrogen (FAN) and intracellular protein analyses revealed higher nitrogen consumption in synthetic media fermentation and greater biomass production in acid hydrolysate media. In addition to isoamyl alcohol (33 mg·L⁻¹), and ethanol (10.18 g·L⁻¹), 1-butanol (61.2 mg·L⁻¹), 1-propanol (13.25 mg·L⁻¹), and acetaldehyde (14.88 mg·L⁻¹) were produced. These results demonstrate the potential of M. guilliermondii to convert corn cob into value-added products.